The human chondrodystrophies represent a genetically heterogeneous group of disorders whose pathogenesis is unknown. This proposal is directed toward the continuation of ongoing studies on the elucidation of the clinical, morphological and biochemical characteristics of these disorders. Cartilage specimens, both normal and chondrodystrophic, will be obtained by rib and iliac crest biopsy. The biopsy specimens will be subjected to histochemical and ultrastructural analysis, the mucopolysaccharide and collagen composition of the matrix determined and metabolic studies performed on liberated chrondrocytes grown in cell culture. The specific aims of this program will be: a) definition of the clinical, radiographic and genetic heterogeneity of the human chondrodystrophies; b) elucidation of the histological, histochemical and ultrastructural characteristics of chondro-osseous tissue from each of them; c) definition of their basic biochemical defects by means of biochemical analysis of cartilage and metabolic studies of cultured chondrocytes; and d) identification of specific animal models of the human chondrodystrophies.